GSK-3 beta activates NF-kappa B to aggravate caerulein-induced early acute pancreatitis in mice

Background: Acute pancreatitis is a life-threatening disease which causes considerable morbidity and mortality. However, no specific and effective treatments are currently available for this critical condition, which is mainly due to the insufficient understanding of the early cellular events in the initial phase of acute pancreatitis. Previous researchers have reported that two independent events, intra-acinar trypsinogen and NF-kappa B activation, are of equal importance in the early development of acute pancreatitis. GSK-3 beta, an essential molecule in multiple physiopathological processes including inflammation, is associated with the expression of the NF-kappa B pathway. Methods: We investigated whether GSK-3 beta affected the expression of cytokines produced by intra-acinar cells and aimed to determine the probable regulatory mechanism by using single allele GSK-3 beta-deficient mice. Results: Our data showed that IL-6 and TNF-alpha mRNA expression in pancreatic tissue and serum IL-6 and TNF-alpha were significantly decreased. Meanwhile, pancreatic phospho-NF-kappa B p65 (ser536) protein expression in GSK-3 beta(+/-) mice was lower than that in wild type (WT) mice. Conclusions: GSK-3 beta may activate intra-acinar NF-kappa B signaling to promote the production of proinflammatory cytokines, which then induces the recruitment of inflammatory cells and activation of the cytokine cascade, further promoting local and systemic inflammation and ultimately aggravating acute pancreatitis. These findings strongly indicate that GSK-3 beta may be a potential treatment target for acute pancreatitis.